Ethyl Acetate → HCID 59698762, compound

HRID 900975Notes

Reaction equation

HRID 900975 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][OH:10])[CH:5]=[N:6][C:7]=1Cl.[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>O.C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][OH:10])[CH:5]=[N:6][C:7]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 21882961(5,6-Dichloropyridin-3-yl)methanol

Product 1

HCID 59698762HCID 59698762, compoundYield 97.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 5,6-dichloro-pyridin-3-yl-methanol (10.0 g, 56.2 mmol), phenylboronic acid (7.5 g, 61.5 mmol), K2CO3 (20.0 g, 145 mmol) in H2O (140 mL) and dimethoxyethane (140 mL, 0.4 M), is degassed and treated with tetrakis(triphenylphosphine)palladium(0) (1.4 g, 1.2 mmol) and warmed to a gentle reflux under nitrogen for 4 h. After cooling to room temperature, ethyl acetate (100 mL) is added and the solids are filtered and washed with ethyl acetate (20 ml). The filtrate is extracted with ethyl acetate (100 mL) and the organic layer is washed with H2O (200 mL), saturated aq NaCl (200 mL) and dried over Na2SO4. The product is purified by MPLC (30-90% ethyl acetate in n-heptane) to provide 5-chloro-6-phenyl-pyridin-3-yl-methanol as a light yellow solid (12.0 g, 97%): Rf 0.24 (30% ethyl acetate in n-heptane), 1H NMR (CDCl3, 300 MHz) δ 8.47 (br s, 1 H), 7.78 (br s, 1 H), 7.70-7.65 (m, 2 H), 7.50-7.40 (m, 3 H), 4.67 (s, 2 H); ESI-LCMS m/z calcd for C12H10ClNO: 219.0; found 220.0 (M+1)+.

Workup

  1. temperaturewarmed to
  2. temperaturea gentle reflux under nitrogen for 4 h
  3. filtrationthe solids are filtered
  4. washwashed with ethyl acetate (20 ml)
  5. extractionThe filtrate is extracted with ethyl acetate (100 mL)
  6. washthe organic layer is washed with H2O (200 mL), saturated aq NaCl (200 mL)
  7. dry with materialdried over Na2SO4
  8. customThe product is purified by MPLC (30-90% ethyl acetate in n-heptane)

Sources & evidence

ORD record
ord-fb7747fddc9643839b372f189aa1a2e2
Source dataset
uspto-grants-2008_04
Patent number
US07361671B2

Reaction notes

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